The study found that GABA, which induces cognitive impairment of depression co-disease in youth, can have synth regulation mechanism

Depression is by far the most common mental illness.
patients with anxiety and cognitive impairment had differences in symptom performance, pathophysiological processes and antidepressant efficacy compared to patients with simple depression, but their potential neurobiological mechanisms needed to be clarified.
previous studies have shown that poor experiences in childhood increase the risk of multiple mental disorders in adults, including depression, anxiety and other forms of affective disorders and cognitive impairment.
Using animal models of youth social frustration stress (ASDS) that are intended to be bullied by human companions, Wang Li, a researcher at the Mental Health Key Laboratory of the Institute of Psychology of the Chinese Academy of Sciences, found that ASDS can stabilize a variety of emotional and cognitive changes in adult animals, accompanied by a decrease in the total amount of brain-induced neurotrophic factors (BDNF) and the transcription level of the promoter IV.
has been extensively reported on the role of BDNF and its subject TrkB in depression and its treatment, but the synthesization process downstream is still unclear.
GABA energy system is the main inhibitory nervous system in the brain and the downstream path of the BDNF-TrkB signaling path.
So on the basis of previous work, the researchers used genetically modified animals, combined with behavior, molecular biology and electrophysiology to further explore the role of GABA downstream of BDNF signals in inhibiting synactical transmission in different depression common disease patterns. the
study found that ASDS led to a range of emotional and cognitive changes in adult animals, including decreased social interest, increased anxiety-like behavior, and impaired cognitive transition function, accompanied by a decrease in mPFC GABA's inhibitory synaptic delivery, which was manifested in a spontaneous inhibitory post-synaptic current (sipsC) release with an average frequency rather than a significant decrease in amplitude.
further detection of GABA signal transducting molecules and found that the mRNA expression level of mPFC GABA synthase G ADD65 was also significantly reduced (Figure 1).
these suggest that youth stress leads to continuous inhibition of GABA function in the brain region.
team's previous work found that the decline in BDNF caused by ASDS was mainly related to the decrease in the level of BDNF IV initiation transcription.
Therefore, using BDNF KIV genetically modified animals, it was found that the specific knockout of BDNF initiator IV can directly lead to behavioral changes characterized by loss of social interest and impairment of cognitive conversion function, and mPFC GABA can inhibit synaptic transmission damage, but have the opposite effect on anxiety-like behavior. The effects, as shown by increased time spent opening the arm in the elevated cross maze and reduced time off the closed arm (Figure 2), suggest that mPFC GABA synaptic delivery may be a downstream mediated pathway for ass-induced cognitive impairment of depressive behavioral co-disease and BDNF signal transducting impairment.
researchers further increased BDNF signaling pathogenic activity by single acute microindulation BDNF TrkB subjectors in model animals, and found that social interest and cognitive impairment induced by youth stress can be quickly restored and mPFC GABA can be reversed for synaptic delivery inhibition, but this improvement does not include anxiety-like behavior (Figure 3).
At the same time, the researchers also used a clinically used antidepressant monoamine oxidase inhibitor (TCP) and found that chronic antidepressant therapy in adulthood also improved social interest and cognitive impairment, but also lacked improved performance for anxiety-like behavior, along with an increase in mRNA expression of GABA synthase GADH67, and the recovery of mPFC GABA synaptic delivery inhibition caused by stress (Figure 4).
these results suggest that GABA downstream of the mPFC BDNF signal can be synaptic transmission mainly involved in the occurrence of cognitive impairment of depression co-disease caused by social stress in youth, rather than depression co-disease anxiety-like behavior.
the study provides a potential target for rapid treatment of cognitive dysfunction in future patients with depression.
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