Abstract
Growth hormone releasing hormone (GHRH) has recently been shown to increase the level of γ-aminobutyric acid (GABA) and activate GABA receptors (GABARs) in the cerebral cortex. GABA is an inhibitory neurotransmitter that can inhibit seizures. Does GHRH enhance the inhibitory effect of GABA to prevent epilepsy by increasing the GABA level and activating GABARs? In this study, patients with epilepsy and C57/BL6 mice with epilepsy induced by kainic acid (KA) or pentylenetetrazol (PTZ) served as the research subjects. Western blots were used to observe the differences in GHRH expression between the normal group and the epilepsy group, immunofluorescence was performed to explore the localization of GHRH in the brain, and coimmunoprecipitation was used to observe the interaction between GHRH and GABARs. GHRH expression was significantly increased in both patients with temporal lobe epilepsy (TLE) and in two mouse models induced by KA or PTZ compared with that in the normal groups (P < 0.05 or P < 0.01). GHRH was expressed in neurons in both humans and mice. Additionally, GHRH co-localized with presynaptic and postsynaptic sites of inhibitory neurons. Coimmunoprecipitation confirmed that GHRH interacted with GABAAα1 and GABAAβ2 + 3. GHRH may play an important role in inhibiting seizures by activating GABAARs.
Highlights
Epilepsy is a common chronic neurological disease caused by the abnormal discharge of neurons in the brain and is characterized by short, rigid, repeated neurological dysfunction[1,2,3]
The primary finding of this study is that Growth hormone releasing hormone (GHRH) expression was significantly increased in the brains of both patients with temporal lobe epilepsy (TLE) and in two mouse models of epilepsy induced by either kainic acid (KA) or PTZ
GHRH has been shown to increase GHRH increases γ-aminobutyric acid (GABA) levels and activate GABA receptors (GABARs) to promote non-rapid eye movement (NREM) sleep, which contributes to the regulation of sleep by growth hormone (GH)
Summary
Epilepsy is a common chronic neurological disease caused by the abnormal discharge of neurons in the brain and is characterized by short, rigid, repeated neurological dysfunction[1,2,3]. The 68th World Health Assembly, which was held on May 26, 2015, unanimously approved the resolution “Global Burden of Epilepsy and the Need for Coordinated Action at the Country Level to Address its Health, Social and Public Knowledge Implications”. This resolution urged member states to implement coordinated action against epilepsy and its consequences[8]. A reduction in GABAergic interneuron activity weakens its suppressive function, thereby increasing the occurrence of spontaneous seizures and promoting the progression of TLE17. Does GHRH increase GABA levels and activate GABARs to protect against epilepsy? We conducted the current study to explore this issue
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