scholarly journals Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3240
Author(s):  
Maria Sidorova ◽  
Golo Kronenberg ◽  
Susann Matthes ◽  
Markus Petermann ◽  
Rainer Hellweg ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Tryptophan Hydroxylase ◽  
Transgenic Rat ◽  
Compensatory Mechanism ◽  
Shrna Expression ◽  
Neurogenic Niche ◽  
Adult Rat ◽  
And Behavior ◽  
Transgenic Rat Model ◽  
Antidepressant Action

Serotonin (5-hydroxytryptamine, 5-HT) is a crucial signal in the neurogenic niche of the hippocampus, where it is involved in antidepressant action. Here, we utilized a new transgenic rat model (TetO-shTPH2), where brain 5-HT levels can be acutely altered based on doxycycline (Dox)-inducible shRNA-expression. On/off stimulations of 5-HT concentrations might uniquely mirror the clinical course of major depression (e.g., relapse after discontinuation of antidepressants) in humans. Specifically, we measured 5-HT levels, and 5-HT metabolite 5-HIAA, in various brain areas following acute tryptophan hydroxylase 2 (Tph2) knockdown, and replenishment, and examined behavior and proliferation and survival of newly generated cells in the dentate gyrus. We found that decreased 5-HT levels in the prefrontal cortex and raphe nuclei, but not in the hippocampus of TetO-shTPH2 rats, lead to an enduring anxious phenotype. Surprisingly, the reduction in 5-HT synthesis is associated with increased numbers of BrdU-labeled cells in the dentate gyrus. At 3 weeks of Tph2 replenishment, 5-HT levels return to baseline and survival of newly generated cells is unaffected. We speculate that the acutely induced decrease in 5-HT concentrations and increased neurogenesis might represent a compensatory mechanism.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

scholarly journals The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrus

2009 ◽  
Vol 29 (7) ◽  
pp. 1408-1421 ◽  
Author(s):  
Woon Ryoung Kim ◽  
Ok-hee Park ◽  
Sukwoo Choi ◽  
Se-Young Choi ◽  
Soon Kwon Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dentate Gyrus ◽  
Neuronal Function ◽  
And Behavior

P3-328: Dissection of physiological and pathological phosphorylation in Axon transgenic rat model of neurofibrillary pathology

2006 ◽  
Vol 2 ◽  
pp. S471-S471
Author(s):  
Miroslava Pevalova ◽  
Jozef Hanes ◽  
Norbert Zilka ◽  
Ludmila Cuninkova ◽  
Martin Cente ◽  
...  
Keyword(s):  
Rat Model ◽  
Transgenic Rat ◽  
Neurofibrillary Pathology ◽  
Transgenic Rat Model

Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat

2012 ◽  
Vol 218 (2) ◽  
pp. 437-453 ◽  
Author(s):  
Angélica Zepeda ◽  
Andrea Aguilar-Arredondo ◽  
Gabriela Michel ◽  
Laura Elisa Ramos-Languren ◽  
Martha L. Escobar ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Functional Recovery ◽  
Focal Lesion ◽  
Structural Reorganization ◽  
Adult Rat

Emx1 and Emx2 functions in development of dorsal telencephalon

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 101-111 ◽  
Author(s):  
M. Yoshida ◽  
Y. Suda ◽  
I. Matsuo ◽  
N. Miyamoto ◽  
N. Takeda ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Expression Patterns ◽  
Lateral Shift ◽  
Cerebral Hemispheres ◽  
Limbic Cortex ◽  
Lateral Region ◽  
Gap Gene ◽  
Positive Region ◽  
Dorsal Telencephalon ◽  
And Behavior

The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty spiracles, and their expression patterns have suggested their involvement in regional patterning of the forebrain. To define their functions we introduced mutations into these loci. The newborn Emx2 mutants displayed defects in archipallium structures that are believed to play essential roles in learning, memory and behavior: the dentate gyrus was missing, and the hippocampus and medial limbic cortex were greatly reduced in size. In contrast, defects were subtle in adult Emx1 mutant brain. In the early developing Emx2 mutant forebrain, the evagination of cerebral hemispheres was reduced and the roof between the hemispheres was expanded, suggesting the lateral shift of its boundary. Defects were not apparent, however, in the region where Emx1 expression overlaps that of Emx2, nor was any defect found in the early embryonic forebrain caused by mutation of the Emx1 gene, of which expression principally occurs within the Emx2-positive region. Emx2 most likely delineates the palliochoroidal boundary in the absence of Emx1 expression during early dorsal forebrain patterning. In the more lateral region of telencephalon, Emx2-deficiency may be compensated for by Emx1 and vice versa. Phenotypes of newborn brains also suggest that these genes function in neurogenesis corresponding to their later expressions.

scholarly journals Substance P Enhances NMDA Channel Function in Hippocampal Dentate Gyrus Granule Cells

1998 ◽  
Vol 80 (1) ◽  
pp. 113-119 ◽  
Author(s):  
David N. Lieberman ◽  
Istvan Mody
Keyword(s):  
Substance P ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Excitatory Amino Acid ◽  
Calcium Influx ◽  
Network Activity ◽  
Hippocampal Dentate Gyrus ◽  
Adult Rat ◽  
Channel Function ◽  
Nmda Channel

Lieberman, David N. and Istvan Mody. Substance P enhances NMDA channel function in hippocampal dentate gyrus granule cells. J. Neurophysiol. 80: 113–119, 1998. Substance P (SP)–containing afferents and the NK-1 tachykinin receptor to which SP binds are present in the dentate gyrus of the rat; however, direct actions of SP on principal cells have not been demonstrated in this brain region. We have examined the effect of SP on N-methyl-d-aspartate (NMDA) channels from acutely isolated dentate gyrus granule cells of adult rat hippocampus to assess the ability of SP to regulate glutamatergic input. SP produces a robust enhancement of single NMDA channel function that is mimicked by the NK-1–selective agonist Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is prevented by the selective NK-1 receptor antagonist (+)-(2 S,3 S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation of protein kinase C were not required for the SP-induced increase in NMDA channel open durations. The dramatic enhancement of excitatory amino acid–mediated excitability by SP places this neuropeptide in a key position to gate activation of hippocampal network activity.

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