Non‐invasive brain stimulation causes anxiolytic effect in intracerebroventricular streptozotocin injected rats through prevention of serotonergic fibres in dorsal hippocampus

Abstract

AbstractBackgroundIntracerebroventricular streptozotocin (ICV‐STZ) injection at 3mg/kg of b/w is reported to induce sporadic Alzheimer disease (sAD) like pathology, where it causes an insulin resistance brain state. Synaptic dysfunction along with glial aggravation poses major risk factor for sAD. Brain stimulation evinced to be promising in AD patients, however, mechanism of the same in the form of magnetic field (MF) stimulation are elusive.MethodTotal 55 rats were recruited and randomly divided into five groups: Control, Sham, AD, Sham+MF, AD+MF. Animals were provided with ad libitum food and water, experiments were performed under permission from IAEC (file no. 937/IAEC/2016). Rats were exposed to 17.96µT for 2hr/day for 30 days and at end elevated plus maze task was performed. Next, transmission electron microscopy(TEM), Golgi‐Cox staining was done on hippocampal sample. In addition, GPx activity and serotonin was measured in hippocampal homogenate.ResultReduction in ratio of time spent in close versus open arm in AD group as compared to Sham (p<0.001), Sham+MF (p<0.01) and AD+MF (p = 0.008). In continuation, head dipping duration was also reduced significantly in AD group as compared to control (p = 0.008), Sham+MF (p = 0.03) and AD+MF (p = 0.001). We found a loss of spine density in apical dendrite of with invasion of ramified microglia in neurovascular‐unit in dCA1 layer of AD group versus control (p<0.0001) and AD+MF(p = 0.004). TEM examination of hippocampal samples, we found invasion of ramified microglia in NVU as well as loss of synaptic density. Furthermore, GPx activity was found to be decreased in AD group (p<0.05) versus other counterparts on 30th day post‐injection of STZ. Similarly, serotonin was depleted in AD group as compared to other groups (p<0.05). In addition, results showed a strong correlation between head dipping duration and serotonin level in AD group on 30th day post‐injection of STZ (r = 0.7;p = 0.02).ConclusionHence, this work reveals that MF stimulation to have anxiolytic effect through replenishing the synaptic dysfunction and serotonin loss in dorsal CA1 pyramidal cells of hippocampus in ICV‐STZ model of sAD.