Gi-DREADD-mediated modulation of astrocyte in the dorsal hippocampus improves working and hippocampus-dependent memory in the unilateral 6-hydroxydopamine lesioned rats.

Cognitive impairment deficits is one of the common non-motor symptoms of Parkinson's disease (PD). Although the mechanism is still unclear, emerging research suggests that the dorsal hippocampus (dHIPP) and astrocyte (AS) may be involved in the cognitive dysfunction in PD. Thus, the effects of Gq or Gi mediated designer receptors exclusively activated by designer drugs (DREADD) manipulation of dHIPP AS on working and hippocampus-dependent memory were investigated in the Morris water maze and hole-board test in sham-operated and unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The results showed that 6-OHDA lesions impaired working and hippocampus-dependent memory, decreased the peak theta (θ) frequency of the dHIPP and the levels of dopamine in the memory-associated brain regions. Although the lesions did not alter the glial fibrillary acidic (GFAP) protein level or the density of GFAP-positive AS in the dHIPP, the AS in the CA1 and CA3 regions of the dHIPP showed increased cell body area and number of primary processes per cell. Gi-DREADD mediated manipulation of dHIPP AS improved working and hippocampus-dependent memory, and increased the peak θ frequency of the dHIPP only in the lesioned rats. It also increased the levels of 5-hydroxytryptamine in some memory-associated brain regions in both sham-operated and the lesioned rats. In contrast, Gq-DREADD mediated manipulation of dHIPP AS had no effects. These results suggest that Gi-DREADD mediated manipulation of dHIPP AS improves working and hippocampus-dependent memory in parkinsonian rats, potentially through an increase in the peak θ frequency in the dHIPP, and that changes in the monoamines also play a role in this process.