... these findings ... implicate loss of hippocampal interneurons in the pathogenesis of schizophrenia...

Hyperactivity of the dopaminergic system is thought to underlie the positive symptoms of schizophrenia. A study by Daniel Lodge and his team at the University of Texas Health Science Center shows that medial ganglionic eminence (MGE) transplants normalize aberrant dopaminergic signalling and behavioural correlates of positive symptoms in a rodent model of schizophrenia. The findings suggest that cell-based therapies are a potential treatment option for this condition.

Although the pathogenesis of dysregulated dopamine signalling in schizophrenia is unknown, hyperactivity in the hippocampal subfields might be involved. This aberrant signalling in the hippocampus could have downstream effects on dopaminergic neurons, resulting in the behavioural and cognitive abnormalities seen in patients, and in animal models of schizophrenia.

GABAergic precursors in the MGE are known to migrate and differentiate into functional interneurons after transplantation in animal models. Lodge's team had already shown that deep brain stimulation could attenuate hippocampal hyperactivity and reverse cognitive deficits in the methylazoxymethanol actetate (MAM) rodent model of schizophrenia. In the current study, they used GFP-labelled MGE tissue transplanted into the ventral hippocampus of MAM-treated rats to enhance GABAergic signalling.

After transplantation, the researchers confirmed the MGE-derived cells as interneurons by electrophysiological recording, and by immunostaining for interneuron and GABAergic cell markers.

The MAM-treated rats transplanted with live cells exhibited normalized hippocampal firing rates compared with controls that received dead cells. Similarly, increased dopaminergic neuron firing in the ventral tegmental area was normalized after live-cell transplants into the MAM-treated animals. These animals also had reduced locomotor activity in response to amphetamine in a standard test of behavioural function.

The findings not only implicate loss of hippocampal interneurons in the pathogenesis of schizophrenia, but also provide evidence that cell transplantation could have positive effects on cognitive function in patients with neuropsychiatric disorders.