Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression
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Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression. / Dósa, Zita; Nieto-Gonzalez, Jose Luis; Elfving, Betina; Hougaard, Karin Sørig; Holm, Mai Marie; Wegener, Gregers; Jensen, Kimmo.
In: Acta Neuropsychiatrica, Vol. 35, No. 6, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression
AU - Dósa, Zita
AU - Nieto-Gonzalez, Jose Luis
AU - Elfving, Betina
AU - Hougaard, Karin Sørig
AU - Holm, Mai Marie
AU - Wegener, Gregers
AU - Jensen, Kimmo
N1 - Publisher Copyright: © Scandinavian College of Neuropsychopharmacology 2023.
PY - 2023
Y1 - 2023
N2 - Objective: Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the fetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Methods: Pregnant rats, exposed to dexamethasone (DEX), a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety-and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABAA receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. Results: The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2, components of the vesicle release machinery. Conclusion: The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.
AB - Objective: Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the fetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Methods: Pregnant rats, exposed to dexamethasone (DEX), a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety-and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABAA receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. Results: The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2, components of the vesicle release machinery. Conclusion: The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.
KW - neuronal plasticity
KW - patch-clamp
KW - Scamp2
KW - Snap-25
KW - Stress
U2 - 10.1017/neu.2023.18
DO - 10.1017/neu.2023.18
M3 - Journal article
C2 - 36896595
AN - SCOPUS:85150390050
VL - 35
JO - Acta Neuropsychiatrica
JF - Acta Neuropsychiatrica
SN - 0924-2708
IS - 6
ER -
ID: 345491635