{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:58:10Z","timestamp":1780901890403,"version":"3.54.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prenatal stress (PS) is a major risk factor for depression later in life, yet the cellular mechanisms linking early-life adversity to long-term affective vulnerability remain incompletely understood. Neuropeptide receptors have emerged as important modulators of stress-related psychopathology, but their roles in mitochondrial regulation within limbic circuits remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A rat model of PS was established to assess depression-like behaviors in adulthood. Mitochondrial ultrastructure, ATP production, and the expression of Galanin receptor 2 (GalR2) and key components of the PINK1\/Parkin mitochondrial quality control machinery were examined in the ventral hippocampus (vHPC). The effects of intranasal administration of the GalR2 agonist AR-M1896 on behavioral and mitochondrial alterations were evaluated\n                      <jats:italic>in vivo<\/jats:italic>\n                      . To directly test whether the vHPC mediates these effects, we performed unilateral intra\u2212vHPC infusion of AR\u2212M1896.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , glucocorticoid exposure and pharmacological manipulation of GalR2 were used to assess their impact on mitochondrial function and PINK1\/Parkin signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PS induced persistent anhedonia-like behavior and behavioral despair phenotypes in adult offspring, accompanied by marked mitochondrial structural abnormalities, reduced ATP production, and downregulation of GalR2 and PINK1\/Parkin-associated mitochondrial quality control signaling in the vHPC. Intranasal AR-M1896 partially normalized reward-related behavioral deficits and ameliorated mitochondrial dysfunction. Importantly, direct intra\u2212vHPC infusion of AR\u2212M1896 elevated ATP, PINK1 and Parkin levels in the ipsilateral vHPC, providing causal evidence that the vHPC is a critical site for GalR2\u2212mediated PINK1\/Parkin-related mitophagy\u2212restoring effects. In cell-based assays, glucocorticoid exposure suppressed, whereas GalR2 activation enhanced, mitochondrial membrane potential and PINK1\/Parkin-related signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify a GalR2\u2013mitochondrial axis in the ventral hippocampus that is disrupted by PS and associated with vulnerability to depression-like phenotypes. The complementary intra\u2212vHPC infusion experiments establish a causal role for vHPC GalR2 signaling in rescuing mitochondrial deficits, directly demonstrating that intranasal AR\u2212M1896 acts at least in part via the vHPC. This receptor\u2013organelle pathway may represent a neurobiological mechanism linking early-life adversity to long-term affective dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1809262","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:05:42Z","timestamp":1780898742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of a GalR2\u2013mitochondrial axis in the ventral hippocampus contributes to depression-like phenotypes after prenatal stress"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingjing","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University","place":["Beijing, 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Disorders, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qing David","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Pathology, Capital Medical University","place":["Beijing, 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