Dataset Information

Specific sub-regions along the longitudinal axis of the hippocampus mediate antidepressant-like behavioral effects.

ABSTRACT: Current antidepressants are suboptimal due incomplete understanding of the neurobiology underlying their behavioral effects. However, imaging studies suggest the hippocampus is a key brain region underpinning antidepressant action. There is increasing attention on the functional segregation of the hippocampus into a dorsal region (dHi) predominantly involved in spatial learning and memory, and a ventral region (vHi) which regulates anxiety, a symptom often co-morbid with depression. However, little is known about the roles of these hippocampal sub-regions in the antidepressant response. Moreover, the area between them, the intermediate hippocampus (iHi), has received little attention. Here, we investigated the impact of dHi, iHi or vHi lesions on anxiety- and depressive-like behaviors under baseline or antidepressant treatment conditions in male C57BL/6 mice (n = 8-10). We found that in the absence of fluoxetine, vHi lesions reduced anxiety-like behavior, while none of the lesions affected other antidepressant-sensitive behaviors. vHi lesions prevented the acute antidepressant-like behavioral effects of fluoxetine in the tail suspension test and its anxiolytic effects in the novelty-induced hypophagia test. Intriguingly, only iHi lesions prevented the antidepressant effects of chronic fluoxetine treatment in the forced swim test. dHi lesions did not impact any behaviors either in the absence or presence of fluoxetine. In summary, we found that vHi plays a key role in anxiety-like behavior and its modulation by fluoxetine, while both iHi and vHi play distinct roles in fluoxetine-induced antidepressant-like behaviors.

SUBMITTER: Levone BR

PROVIDER: S-EPMC8100619 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less-known. We found that an epigenetic and energetic agent, acetyl-L-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line (FSL) rats. After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not respond (nrFSL). RNAseq for the ventral dentate-gyrus (vDG), a mood-regulatory region, identified metabolic factors as key markers predisposing to depression (insulin receptors Insr, glucose transporters Glut-4 and Glut-12, the regulator of appetite Cartpt) and to LAC responsiveness (leptin receptors Lepr, metabotropic glutamate receptors-2 mGlu2, neuropeptide-Y NPY, and mineralocorticoid receptors MR). Furthermore, we found that stress-induced treatment-resistance in nrFSL shows a new gene profile, including the metabolic regulator factors Elovl7 and Cyb5r2 and the synaptic regulator NPAS4. Finally, while improving central energy regulation and exerting rapid antidepressant-like effects, LAC corrected a systemic hyperinsulinemia and hyperglycemia.tance in rFSL and failed to do that in nrFSL. These findings establish CNS energy regulation as factor to be considered for the development of better therapeutics. Agents, like LAC, which regulate metabolic factors and reduce glutamate overflow, could rapidly ameliorate depression and could also be considered for treatment of insulin-resistance in depressed subjects. The approach here serves as a model for identifying markers and underlying mechanisms of predisposition to diseases and treatment responsiveness that may be useful in translation to human behavior and psychopathology. Ventral dentate gyrus RNA from 3 biological replicates per group (vehicle-FRL, vehicle-FSL, LAC-treated not-responder FSL, LAC-treated responder FSL, all males) was used for library prep (TruSeq Stranded Total RNA with Ribo-Zero Human/Mouse/Rat) and sequenced on Illumina HiSeq2500 at the Genomic Core facility at The Rockefeller University. Each sample was provided with a unique adapter and all samples were put in the same pool and run in multiple lanes to control for lane effects with a sequencing depth of about 30M (100bp, single).

Dataset Information

Specific sub-regions along the longitudinal axis of the hippocampus mediate antidepressant-like behavioral effects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets