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.

scholarly journals Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

2009 ◽  
Vol 102 (4) ◽  
pp. 2194-2207 ◽  
Author(s):  
David Murchison ◽  
Angelika N. McDermott ◽  
Candi L. LaSarge ◽  
Kathryn A. Peebles ◽  
Jennifer L. Bizon ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Cognitive Status ◽  
Cognitively Impaired ◽  
Aged Rats ◽  
Middle Aged ◽  
Cholinergic Basal Forebrain ◽  
Age Related ◽  
Forebrain Neurons ◽  
Firing Properties

Alterations in neuronal Ca2+ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca2+ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca2+ current recording with Ca2+-sensitive ratiometric microfluorimetry to measure Ca2+ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca2+ channel currents. However, Ca2+ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca2+ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca2+ buffering by cholinergic basal forebrain neurons may be important during aging.

Effects of Intraventricular Encapsulated Hngf-Secreting Fibroblasts in Aged Rats

1996 ◽  
Vol 5 (2) ◽  
pp. 205-223 ◽  
Author(s):  
Mark D. Lindner ◽  
Cristin E. Kearns ◽  
Shelley R. Winn ◽  
Beata Frydel ◽  
Dwaine F. Emerich
Keyword(s):  
Morris Water Maze ◽  
Basal Forebrain ◽  
Water Maze ◽  
Genetically Modified ◽  
Learning Task ◽  
Activity Levels ◽  
Aged Rats ◽  
Semipermeable Membranes ◽  
Age Related ◽  
Forebrain Neurons

Exogenous NGF administered into the central nervous system (CNS) has been reported to improve cognitive function in aged rats. However, concerns have been expressed about the risks involved with supplying NGF to the CNS. In this study, baby hamster kidney cells (BHK) genetically modified to secrete human NGF (hNGF) were encapsulated in semipermeable membranes and implanted intraventricularly. ChAT/LNGFR-positive basal forebrain neurons were shown to atrophy and degenerate with age, especially in cognitively impaired rats. The encapsulated BHK-NGF cells produced less than 10% of doses previously reported to be effective, but this was sufficient to increase the size of ChAT/LNGFR-positive basal forebrain neurons in the aged and learning-impaired rats to the size of the neurons in young healthy rats. The hNGF from these encapsulated cells also improved performance in a repeated-acquisition version of the Morris water maze spatial learning task in learning-impaired 20.6- and 26.7- mo-old rats. Furthermore, there was no evidence that these doses of hNGF impaired Morris water maze performance in the youngest 3.3-5.4 mo rats, and analyses of mortality rates, body weights, somatosensory thresholds, potential hyperalgesia, and activity levels, suggested that these levels of exogenous hNGF are not toxic or harmful to aged rats. These results suggest that CNS-implanted semipermeable membranes, containing genetically modified xenogeneic cells continuously producing these levels of hNGF, attenuate age-related cognitive deficits in nonimmunosuppressed aged rats, and that both the surgical implantation procedure and long-term exposure to low doses of hNGF appear safe in aged rats.

scholarly journals Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ashley M. Fortress ◽  
Mona Buhusi ◽  
Kris L. Helke ◽  
Ann-Charlotte E. Granholm
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Memory Impairments ◽  
Age Related ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Cholinergic Degeneration ◽  
And Function ◽  
Do So

Learning and memory impairments occurring with Alzheimer's disease (AD) are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs). BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF) which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the firstin vivoevidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors.

Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats

2017 ◽  
Vol 170 ◽  
pp. 93-99 ◽  
Author(s):  
Daniel G. Kougias ◽  
Emily R. Hankosky ◽  
Joshua M. Gulley ◽  
Janice M. Juraska
Keyword(s):  
Water Maze ◽  
Male Rats ◽  
Maze Performance ◽  
Age Related

scholarly journals Icariin Promotes Survival, Proliferation, and Differentiation of Neural Stem Cells In Vitro and in a Rat Model of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Denglei Ma ◽  
Lihong Zhao ◽  
Li Zhang ◽  
Yali Li ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Basal Forebrain ◽  
Chinese Herb ◽  
Cholinergic Neurons ◽  
Model Of Alzheimer’S Disease ◽  
Promising Therapeutic Approach ◽  
Proliferation And Differentiation

Alzheimer’s disease (AD) involves the degeneration of cholinergic neurons in the basal forebrain. Neural stem cell (NSC) transplantation has emerged as a promising therapeutic approach for treating AD. Icariin (ICA) is the main active component in Epimedium, a traditional Chinese herb. The purpose of the present study was to investigate the effects and mechanisms of ICA on the proliferation and differentiation of NSCs in the basal forebrain of a fimbria-fornix transection (FFT) rat model. In the present study, ICA promoted the survival, proliferation, and migration of NSCs in vitro. In FFT rats, ICA promoted the proliferation and differentiation of NSCs into neurons and increased the number of cholinergic neurons in the MS and VDB of the basal forebrain. These results suggest that combination therapy of ICA oral administration and NSC transplantation may provide a new potential and effective approach for AD therapy.

Amyloid-b1-42 treatment does not have a specific effect on cholinergic neurons in in vitro basal forebrain neuronal cultures of rat

2002 ◽  
Vol 53 (3) ◽  
pp. 257-265 ◽  
Author(s):  
Henrietta Papp ◽  
P. Jr. Kása ◽  
Magdolna Pákáski ◽  
L. Baláspiri ◽  
P. Sr. Kása
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Specific Effect ◽  
Neuronal Cultures

Paternal Δ9-Tetrahydrocannabinol Exposure Prior to Mating Elicits Deficits in Cholinergic Synaptic Function in the Offspring

2020 ◽  
Vol 174 (2) ◽  
pp. 210-217
Author(s):  
Theodore A Slotkin ◽  
Samantha Skavicus ◽  
Edward D Levin ◽  
Frederic J Seidler
Keyword(s):  
Brain Development ◽  
Choline Acetyltransferase ◽  
Drug Exposure ◽  
Brain Regions ◽  
Synaptic Function ◽  
Male Rats ◽  
High Dose ◽  
Age Related ◽  
The Impact ◽  
Ach Receptors

Abstract Little attention has been paid to the potential impact of paternal marijuana use on offspring brain development. We administered Δ9-tetrahydrocannabinol (THC, 0, 2, or 4 mg/kg/day) to male rats for 28 days. Two days after the last THC treatment, the males were mated to drug-naïve females. We then assessed the impact on development of acetylcholine (ACh) systems in the offspring, encompassing the period from the onset of adolescence (postnatal day 30) through middle age (postnatal day 150), and including brain regions encompassing the majority of ACh terminals and cell bodies. Δ9-Tetrahydrocannabinol produced a dose-dependent deficit in hemicholinium-3 binding, an index of presynaptic ACh activity, superimposed on regionally selective increases in choline acetyltransferase activity, a biomarker for numbers of ACh terminals. The combined effects produced a persistent decrement in the hemicholinium-3/choline acetyltransferase ratio, an index of impulse activity per nerve terminal. At the low THC dose, the decreased presynaptic activity was partially compensated by upregulation of nicotinic ACh receptors, whereas at the high dose, receptors were subnormal, an effect that would exacerbate the presynaptic defect. Superimposed on these effects, either dose of THC also accelerated the age-related decline in nicotinic ACh receptors. Our studies provide evidence for adverse effects of paternal THC administration on neurodevelopment in the offspring and further demonstrate that adverse impacts of drug exposure on brain development are not limited to effects mediated by the embryonic or fetal chemical environment, but rather that vulnerability is engendered by exposures occurring prior to conception, involving the father as well as the mother.

Age-related release of prolactin by the pituitary and the pituitary-hypothalamic complex in vitro: an attempt to describe the development of the hypothalamic prolactin-inhibiting and -releasing activities in male rats

1987 ◽  
Vol 115 (3) ◽  
pp. 405-409 ◽  
Author(s):  
S. Karanth ◽  
A. Dutt ◽  
H. S. Juneja
Keyword(s):  
Pituitary Gland ◽  
Male Rats ◽  
Inhibiting Activity ◽  
Serum Concentrations ◽  
Developmental Patterns ◽  
Age Related ◽  
Hypothalamic Control ◽  
The Difference

ABSTRACT We have recently demonstrated that the pituitary hypothalamic complex (PHC) is a good model for studying interactions between the hypothalamus and pituitary in vitro. The amount of prolactin secreted by the PHC is an index of prolactin secreted by the pituitary in the presence of hypothalamic control, while the amount released by the whole pituitary alone is an index of prolactin secreted in the absence of hypothalamic control. The amount of prolactin secreted by the PHC has been regarded as an index of hypothalamic prolactin-releasing activity (HPRA), while the difference in the amounts of prolactin secreted by the whole pituitary and the PHC is the hypothalamic prolactin-inhibiting activity (HPIA). Attempts were made to correlate HPRA and HPIA to the development of serum concentrations of prolactin from days 7 to 77 in male rats. The HPRA increased steadily from days 7 to 56, decreased significantly on day 63 and thereafter remained unchanged until day 77. The HPIA was low on days 7 and 14 and increased steadily up to day 49, with no further significant variations. The developmental patterns of HPRA and HPIA were comparable up to day 49. Serum concentrations of prolactin increased significantly until day 28 and remained fairly constant until day 49. The weight of the pituitary gland increased from 1·0± 0·03 mg (mean ± s.e.m.) on day 7 to 7·76 ± 0·32 mg on day 63 and remained unchanged thereafter. The weight of the hypothalamic islet was 31·5 ± 2·88 mg on day 7, 34·83 ±1·45 mg on day 14 and 50·4 ± 4·01 mg on day 21. After day 21 the weights of the hypothalamic islets were not significantly altered, except on day 49. It was concluded that serum concentrations of prolactin are regulated by interaction or competition between HPRA and HPIA at the level of the pituitary. J. Endocr. (1987) 115, 405–409

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