scholarly journals Exogenous NGF Affects Cholinergic Transmitter Function and Y-Maze Behavior in Aged Fischer 344 Male Rats

1991 ◽  
Vol 18 (S3) ◽  
pp. 403-407 ◽  
Author(s):  
Lawrence R. Williams ◽  
R. Jane Rylett ◽  
Hylan C. Moises ◽  
Andrew H. Tang
Keyword(s):  
Brightness Discrimination ◽  
Cholinergic Neurons ◽  
Male Rats ◽  
Neuronal Markers ◽  
Fischer 344 ◽  
Cognitive Measure ◽  
Age Related ◽  
Y Maze ◽  
Cholinergic Phenotype ◽  
The Brain

ABSTRACT:Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age-related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest.effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function.

Abstract WMP45: Manipulation of the Microbiome Improves Functional Recovery After Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Michal Jandzinski ◽  
Venugopal Venna ◽  
Anjali Chauhan ◽  
Joerg Graf ◽  
Louise D McCullough
Keyword(s):  
Functional Recovery ◽  
Artery Occlusion ◽  
Peripheral Tissues ◽  
Aged Mice ◽  
Age Related ◽  
Y Maze ◽  
Obesity Hypertension ◽  
Inflammatory Milieu ◽  
Gastro Intestinal Tract ◽  
The Brain

Background: Circulating inflammatory markers increase with age. This pro-inflammatory milieu makes the organism less capable of coping with stressors such as stroke. Age related inflammation occurs in both the brain and peripheral tissues like the gastro-intestinal tract. There is increasing recognition that commensal bacteria in the GI tract are altered with age or with germ-free housing, affecting the brain. The change occurs most notably in the ratio of two major phyla of the microbiome, the Firmicutes and Bacteroidetes . Young age is associated with a low ratio of the two but this ratio increases with age, which has been linked to many diseases including obesity, hypertension, and diabetes which are major risk factors for stroke. Hypothesis: We hypothesized that there would be age-related differences in the microbiome, and that restoration of a young microbiome would improve functional recovery in aged mice. Methods: Fecal transplants from young and aged donors were administered to recipient animals after suppression of endogenous microbial compositions through concentrated Streptomycin. This allowed for successful colonization of the gut with the newly transplanted microbiome. A transient middle cerebral artery occlusion (MCAO) was used in young (3-4 month) and aged (18-20 month) male mice 4 weeks after transplant. Functional recovery was assessed by neurological deficit scores, the hang wire test, and open field activity. The Y-maze was used to assess cognitive impairment. Results: We successfully reversed the microbiomes of aged organisms and gave young animals “aged” biomes. Animals with “aged” microbiomes prior to stroke had worsened functional recovery based on all behavioral tests. The “aged” biome increased mortality rates most notably in the young recipients which had over 50% mortality. Aged mice had significantly improved functional recovery as assessed by the HW test ( P < 0.05 ) and NDS after reconstitution of “young” microbiome prior to stroke compared to aged control animals with the normal “aged” microbiomes. Conclusion: Aged mice have high Firmicutes and Bacteroidetes relative abundances. Manipulation of the microbiome in young and aged mice is possible. Restoration of a youthful biome improved functional recovery in aged mice.

Circulating hyaluronan levels in the rodent: effects of age and diet

1995 ◽  
Vol 268 (4) ◽  
pp. C952-C957 ◽  
Author(s):  
J. Yannariello-Brown ◽  
S. H. Chapman ◽  
W. F. Ward ◽  
T. C. Pappas ◽  
P. H. Weigel
Keyword(s):  
Fish Meal ◽  
Caloric Intake ◽  
Protein Source ◽  
Male Rats ◽  
Semisynthetic Diet ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats ◽  
Ad Libitum ◽  
Age Related Changes

Circulating hyaluronan (HA) levels were investigated as a function of age and diet in Fischer 344 male rats. A biphasic pattern of age-related changes was observed in rats fed ad libitum a diet in which the protein source was soya/fish meal. HA levels in 3- to 6- and 22- to 29-mo-old rats were not statistically different. However, HA levels in 12- to 20-mo-old rats were 10-29% of the levels in younger or aged adults. HA levels were also measured in rats fed ad libitum a semisynthetic diet in which the protein source was hydrolyzed casein. Whereas the two colonies exhibited similar biphasic age-related changes, HA levels differed 4- to 20-fold at every age examined. Caloric restriction affected HA levels in 19-mo-old casein-fed rats; HA levels were 2.3 times higher than age-matched controls and were not statistically different from young or aged animals. Serum and plasma HA levels were identical in the same individuals at all ages tested. These data suggest that HA turnover and metabolism in the rat are affected by age, dietary composition, and caloric intake.

scholarly journals Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age.

1978 ◽  
Vol 78 (2) ◽  
pp. 319-337 ◽  
Author(s):  
D L Schmucker ◽  
J S Mooney ◽  
A L Jones
Keyword(s):  
Endoplasmic Reticulum ◽  
Fine Structure ◽  
Surface Area ◽  
Structural Parameters ◽  
Male Rats ◽  
Ground Substance ◽  
Stereological Analysis ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats

Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1, 6, 10, 16, 20, 25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume. The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) there are remarkable similarities in hepatocyte ultrastructure between very young and senescent animals, including cell size and the amount of SER.

Selective age-related changes in neuronal markers and smooth muscle reactivity in cerebrovascular beds of Fischer 344 rats

1990 ◽  
Vol 11 (6) ◽  
pp. 631-639 ◽  
Author(s):  
Edith Hamel ◽  
Christine Assumel-Lurdin ◽  
Michèle Bouloy ◽  
Eric T. MacKenzie
Keyword(s):  
Smooth Muscle ◽  
Fischer 344 Rats ◽  
Neuronal Markers ◽  
Fischer 344 ◽  
Age Related ◽  
Age Related Changes

scholarly journals Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats

1998 ◽  
pp. 316-321 ◽  
Author(s):  
F Bernardi ◽  
C Salvestroni ◽  
E Casarosa ◽  
RE Nappi ◽  
A Lanzone ◽  
...  
Keyword(s):  
Brain Cortex ◽  
Steroid Hormone ◽  
Serum Testosterone ◽  
Male Rats ◽  
Endocrine Glands ◽  
Brain Areas ◽  
Age Related ◽  
Specific Radioimmunoassay ◽  
The Brain ◽  
Related Increase

OBJECTIVE: Allopregnanolone is a potent neuroactive steroid hormone produced in the brain and in peripheral endocrine glands. The present study investigated possible age-related variations in allopregnanolone content in brain areas, endocrine glands and serum of male rats. DESIGN: Wistar male rats were categorized into 5 groups (6 rats in each) according to age: 6, 12, 16, 18 and 20 months respectively. METHODS: Allopregnanolone content in acidic homogenates of brain cortex, hypothalamus, pituitary, adrenals and gonads was measured by a specific radioimmunoassay. Serum allopregnanolone, corticosterone and testosterone were also assayed by radioimmunoassay. RESULTS: Brain cortex allopregnanolone content decreased significantly with age, while hypothalamic allopregnanolone content remained constant until 18 months and increased significantly at 20 months. Pituitary content showed a significant age-related reduction. Adrenal allopregnanolone content remained constant until 18 months, and was significantly higher at 20 months. Testis and serum allopregnanolone contents showed significant age-related increases. Serum testosterone levels showed an age-related decrease, while no age-related variation in serum corticosterone was found. CONCLUSIONS: The present study showed a significant impact of aging on allopregnanolone contents in brain, endocrine glands and serum, showing an age-related decrease in brain cortex and pituitary, and an age-related increase in testes, adrenals and serum.

scholarly journals Postweaning Iron Deficiency in Male Rats Leads to Long-Term Hyperactivity and Decreased Reelin Gene Expression in the Nucleus Accumbens

2019 ◽  
Author(s):  
Noriko Nishikura ◽  
Kodai Hino ◽  
Tomoko Kimura ◽  
Yasuhiro Uchimura ◽  
Shinjiro Hino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Iron Deficiency ◽  
Male Rats ◽  
Juvenile Period ◽  
Synaptic Density ◽  
Adequate Diet ◽  
Age Related ◽  
The Brain

ABSTRACT Background Epidemiological research indicates that iron deficiency (ID) in infancy correlates with long-term cognitive impairment and behavioral disturbances, despite therapy. However, the mechanisms underlying these effects are unknown. Objective We investigated how ID affected postweaning behavior and monoamine concentration in rat brains to determine whether ID during the juvenile period affected gene expression and synapse formation in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Methods Fischer 344/Jcl postweaning male rats aged 21–39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. After day 39, all rats were fed the iron-adequate diet. The locomotor activity was evaluated by the open field and elevated plus maze tests at 8 and 12 wk of age. Monoamine concentrations in the brain were analyzed using HPLC at 9 and 13 wk of age. Comprehensive gene expression analysis was performed in the PFC and NAcc at 13 wk of age. Finally, we investigated synaptic density in the PFC and NAcc by synaptophysin immunostaining. Results Behavioral tests revealed a significant reduction of the age-related decline in the total distance traveled in ID rats compared with CN rats (P < 0.05), indicating that ID affected hyperactivity, which persisted into adulthood (13 wk of age). At this age, reelin (Reln) mRNA expression (adjusted P < 0.01) decreased and synaptic density (P < 0.01) increased in the NAcc in the ID group. Regarding the mesolimbic pathway, homovanillic acid concentration increased in the NAcc, whereas the dopamine concentration decreased in the ventral midbrain. Conclusions Our results suggest that ID during the postweaning period in male rats, despite complete iron repletion following ID, led to long-term hyperactivity via monoamine disturbance in the brain and an alteration in the synaptic plasticity accompanied by downregulation of Reln expression in the NAcc.

scholarly journals Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers

2021 ◽  
Vol 13 ◽  
Author(s):  
Sumonto Mitra ◽  
Giorgio Turconi ◽  
Taher Darreh-Shori ◽  
Kärt Mätlik ◽  
Matilde Aquilino ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cholinergic Neurons ◽  
Lewy Body Dementia ◽  
Cholinergic Transmission ◽  
Expression Of Genes ◽  
Age Related ◽  
Y Maze ◽  
In The Wild ◽  
And Function ◽  
Cholinergic Markers

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.

scholarly journals Characterization of age-related changes in synaptic transmission onto F344 rat basal forebrain cholinergic neurons using a reduced synaptic preparation

2014 ◽  
Vol 111 (2) ◽  
pp. 273-286 ◽  
Author(s):  
William H. Griffith ◽  
Dustin W. DuBois ◽  
Annette Fincher ◽  
Kathryn A. Peebles ◽  
Jennifer L. Bizon ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Basal Forebrain ◽  
Water Maze ◽  
Cholinergic Neurons ◽  
Cognitive Status ◽  
Synaptic Function ◽  
Male Rats ◽  
Patch Clamp Recording ◽  
Age Related

Basal forebrain (BF) cholinergic neurons participate in a number of cognitive processes that become impaired during aging. We previously found that age-related enhancement of Ca2+ buffering in rat cholinergic BF neurons was associated with impaired performance in the water maze spatial learning task (Murchison D, McDermott AN, Lasarge CL, Peebles KA, Bizon JL, and Griffith WH. J Neurophysiol 102: 2194–2207, 2009). One way that altered Ca2+ buffering could contribute to cognitive impairment involves synaptic function. In this report we show that synaptic transmission in the BF is altered with age and cognitive status. We have examined the properties of spontaneous postsynaptic currents (sPSCs) in cholinergic BF neurons that have been mechanically dissociated without enzymes from behaviorally characterized F344 rats. These isolated neurons retain functional presynaptic terminals on their somata and proximal dendrites. Using whole cell patch-clamp recording, we show that sPSCs and miniature PSCs are predominately GABAergic (bicuculline sensitive) and in all ways closely resemble PSCs recorded in a BF in vitro slice preparation. Adult (4–7 mo) and aged (22–24 mo) male rats were cognitively assessed using the water maze. Neuronal phenotype was identified post hoc using single-cell RT-PCR. The frequency of sPSCs was reduced during aging, and this was most pronounced in cognitively impaired subjects. This is the same population that demonstrated increased intracellular Ca2+ buffering. We also show that increasing Ca2+ buffering in the synaptic terminals of young BF neurons can mimic the reduced frequency of sPSCs observed in aged BF neurons.

Ultrastructural Localization of Acetylcholinesterase in the Arcuate Nucleus and Median Eminence of the Rat

1977 ◽  
Vol 35 ◽  
pp. 440-441
Author(s):  
K.A. Carson ◽  
C.B. Nemeroff ◽  
M.S. Rone ◽  
J.S. Kizer ◽  
J.S. Hanker
Keyword(s):  
Choline Acetyltransferase ◽  
Median Eminence ◽  
Arcuate Nucleus ◽  
Cholinergic Neurons ◽  
Ultrastructural Localization ◽  
Male Rats ◽  
Neonatal Rats ◽  
Good Marker ◽  
Chemical Studies ◽  
High Doses

Biochemical, physiological, pharmacological, and more recently enzyme histo- chemical data have indicated that cholinergic circuits exist in the hypothalamus. Ultrastructural correlates of these pathways such as acetylcholinesterase (AchE) positive neurons in the arcuate nucleus (ARC) and stained terminals in the median eminence (ME) have yet to be described. Initial studies in our laboratories utilizing chemical lesioning and microdissection techniques coupled with microchemical and light microscopic enzyme histo- chemical studies suggested the existence of cholinergic neurons in the ARC which project to the ME (1). Furthermore, in adult male rats with Halasz deafferentations (hypothalamic islands composed primarily of the isolated ARC and the ME) choline acetyltransferase (ChAc) activity, a good marker for cholinergic neurons, was not significantly reduced in the ME and was only somewhat reduced in the ARC (2). Treatment of neonatal rats with high doses of monosodium 1-glutamate (MSG) results in a lesion largely restricted to the neurons of the ARC.

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

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