Probiotics Treatment Improves Hippocampal Dependent Cognition in a Rodent Model of Parkinson’s Disease

Caroline Xie,Asheeta A. Prasad

doi:10.3390/microorganisms8111661

Abstract

Parkinson’s disease (PD) is a neurological disorder with motor dysfunction and a number of psychiatric symptoms. Symptoms such as anxiety and cognitive deficits emerge prior to motor symptoms and persist over time. There are limited treatments targeting PD psychiatric symptoms. Emerging studies reveal that the gut microbe is altered in PD patients. Here we assessed the effect of a probiotic treatment in a rat model of PD. We used the neurotoxin (6-hydroxydopamine, 6-OHDA) in a preclinical PD model to examine the impact of a probiotic treatment (Lacticaseibacillus rhamnosus HA-114) on anxiety and memory. Rats underwent either sham surgery or received 6-OHDA bilaterally into the striatum. Three weeks post-surgery, rats were divided into three experimental groups: a sham group that received probiotics, a 6-OHDA group that received probiotics, and the third group of 6-OHDA received the placebo formula. All rats had access to either placebo or probiotics formula for 6 weeks. All groups were assessed for anxiety-like behaviour using the elevated plus maze. Cognition was assessed for both non-hippocampal and hippocampal dependent tasks using the novel object recognition and novel place recognition. We report that the 6-OHDA lesion induced anxiety-like behaviour and deficits in hippocampal dependent cognition. Interestingly, the probiotics treatment had no impact on anxiety-like behaviour but selectively improved hippocampal dependent cognition deficits. Together, the results presented here highlight the utility of animal models in examining the neuropsychiatric symptoms of PD and the potential of probiotics as adjunctive treatment for non-motor symptoms of PD.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disorder, hallmarked by the loss of dopamine neurons in the substantia nigra (SN) [1]
Anxiety and cognitive impairments are highly prevalent in PD populations, with 60% of PD patients reporting anxiety, 80% reporting cognitive deficits, and dementia affecting over 80% of PD patients [2,4,6,11,12,13]
Replicating past studies of the 6-OHDA model of PD, we found an increase in anxiety-like behaviour in dopamine lesioned animals when tested on the elevated plus maze (EPM) [23,60]

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder, hallmarked by the loss of dopamine neurons in the substantia nigra (SN) [1]. PD patients suffer from a number of neuropsychiatric symptoms including cognitive impairment, sleep disorders, anxiety, and depression [2,3,4,5,6,7,8,9]. To dissociate neuropsychiatric symptoms from motor deficits, it is crucial to deplete a subset of dopamine neurons, as direct administration of 6-OHDA into the SN either unilaterally or bilaterally leads to severe motor symptoms [20,21]. Induction of partial dopamine depletion by administering 6-OHDA into the striatum has been reliably applied to study neuropsychiatric symptoms of anxiety, cognitive deficits, and motivation [22,23,24,25,26,27,28,29,30,31]. Induction of partial dopamine depletion by administering 6-OHDA into the striatum has been reliably applied to study neuropsychiatric symptoms of anxiety, cognitive deficits, and motivation [22,23,24,25,26,27,28,29,30,31]. 6-OHDA is taken up by DAT and expressed on nigral neurons projecting the striatum, retrogradely depleting nigrostriatal neurons [24,30,32]

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