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Parkinson's disease (PD) is usually characterized by cardinal motor impairments. However, a range of non-motor symptoms precede the motor-phase and are major determinants for the quality of life. To date, no disease modifying treatment is available for PD patients. The gold standard therapy of levodopa is based on restoring dopaminergic neurotransmission, thereby alleviating motor symptoms, whereas non-motor symptoms remain undertreated. One of the most common non-motor symptoms is gastrointestinal dysfunction usually associated with alpha-synuclein accumulations and low-grade mucosal inflammation in the enteric nervous system. Accumulating evidence suggest that the enteric nervous system is involved in PD pathological progression towards the central nervous system. Moreover, different components of the gut could provide a central role in the gut-brain axis, which is as a bidirectional communicational system between the gastrointestinal tract and central nervous system. Dietary components might influence the gut-brain axis by altering microbiota composition or by affecting neuronal functioning in both the ENS and the CNS. This review gives a comprehensive overview of the evidences supporting the hypothesis that PD could initiate in the gut. We also consider how food-based therapies might then have an impact on PD pathology and/or improve non-motor as well as motor symptoms in PD., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Dietary fish oil, providing n3 polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), associates with reduced dementia risk in epidemiological studies and reduced amyloid accumulation in Alzheimer mouse models. We now studied whether additional nutrients can improve the efficacy of fish oil in alleviating cognitive deficits and amyloid pathology in APPswe/PS1dE9 transgenic and wild-type mice. We compared four isocaloric (5% fat) diets. The fish oil diet differed from the control diet only by substituted fish oil. Besides fish oil, the plant sterol diet was supplemented with phytosterols, while the Fortasyn diet contained as supplements precursors and cofactors for membrane synthesis, viz. uridine-monophosphate; DHA and EPA; choline; folate; vitamins B6, B12, C and E; phospholipids and selenium. Mice began the special diets at 5 months and were sacrificed at 14 months after behavioral testing. Transgenic mice, fed with control chow, showed poor spatial learning, hyperactivity in exploring a novel cage and reduced preference to explore novel odors. All fish-oil-containing diets increased exploration of a novel odor over a familiar one. Only the Fortasyn diet alleviated the spatial learning deficit. None of the diets influenced hyperactivity in a new environment. Fish-oil-containing diets strongly inhibited β- and γ-secretase activity, and the plant sterol diet additionally reduced amyloid-β 1-42 levels. These data indicate that beneficial effects of fish oil on cognition in Alzheimer model mice can be enhanced by adding other specific nutrients, but this effect is not necessarily mediated via reduction of amyloid accumulation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The prefrontal cortex has traditionally been implicated in a variety of cognitive processes, including memory, attention and decision making. The detection of effects of prefrontal cortex lesions on attention has been shown to depend on the procedure used to assess the attentional process. We therefore investigated the effects of lesions of the prefrontal cortex in two different visual attention tasks, i.e. a three-choice serial reaction time task involving sustained and divided attention processes and a visual timing task involving sustained attention and response inhibition processes. In two rat strains that are frequently used in behavioural analysis, i.e. albino Wistar rats and pigmented Lister Hooded rats, lesions of the medial prefrontal cortex caused a deterioration of performance in both tasks, although the effect lasted much longer in the visual timing task. This latter task proved to be especially sensitive to detect the consequences of medial prefrontal cortex lesions, consisting of a loss of both attention control and response inhibition. In both attention tasks, Wistar rats performed less accurate and made more anticipatory responses than Listers. Strain differences could not entirely be attributed to possible visual deficits in albinos, which was also evident when locomotor activity in an open field and food-motivated behaviour in a hoarding paradigm were assessed. Due to slower habituation rates, Lister rats were more active and displayed little food hoarding behaviour. In Wistar rats, hoarding was disrupted by medial prefrontal cortex lesions, showing the effectiveness of the lesion. The results indicate that, although different rat strains provide different baseline levels of behaviour for testing lesion- or drug-induced behavioural changes, lesions of the medial prefrontal cortex do not only disrupt sustained attention processes, but also induce a strong impairment in response inhibition in both Wistar and Lister rats.

Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition and latent inhibition. The present study investigated, in rats, the effects of increasing dopamine receptor activation within the medial prefrontal cortex by local administration of the dopamine receptor agonist apomorphine (9 microg/side) on prepulse inhibition and latent inhibition, as well as on spontaneous and amphetamine-induced activity. Apomorphine infusions decreased spontaneous locomotor activity and blocked amphetamine-induced increase in locomotor activity in the open field, which is in line with the suggestion that dopamine receptor activation in the medial prefrontal cortex inhibits mesolimbic dopamine activity. However, apomorphine infusions induced a disruption of prepulse inhibition, an effect associated with increased dopaminergic activity in the nucleus accumbens, and left the latent inhibition effect intact. While these results support previous evidence that the medial prefrontal cortex is a component of the neural circuitry mediating prepulse inhibition but plays no role in latent inhibition, they show that dopamine receptor activation in the medial prefrontal cortex of the rat produces behavioural outcomes that cannot be explained by postulating a simple reciprocal relationship between the mesocortical and mesolimbic dopamine systems.

Latent inhibition is a measure of retarded conditioning to a previously presented nonreinforced stimulus that is impaired in schizophrenic patients and in rats treated with amphetamine. In terms of neural substrates, latent inhibition depends on the integrity of the nucleus accumbens and the inputs to this structure from the hippocampal formation and adjacent cortical areas. Since another major source of input to the nucleus accumbens is the medial prefrontal cortex, and there are numerous demonstrations that manipulations of this region can modify ventral striatal dopamine, we investigated the effects of N-methyl-D-aspartate lesion to the medial prefrontal cortex on latent inhibition, assessed in an off-baseline conditioned emotional response procedure in rats licking for water. In addition, the effects of the medial prefrontal cortex lesion were assessed on a battery of tasks potentially sensitive to medial prefrontal cortex damage, including spontaneous and amphetamine-induced activity, elevated plus maze exploration, food hoarding, prepulse inhibition, and active avoidance. The lesion decreased hoarding behaviour and increased spontaneous exploratory activity in the open field, while exerting only mild effects on amphetamine-induced activity. Prepulse inhibition, exploration of the elevated plus maze, and the acquisition of two-way active avoidance were unaffected by the lesion. Likewise, latent inhibition was left intact following the lesion, suggesting that neither the destruction of the intrinsic cells of the medial prefrontal cortex nor any potential lesion-induced changes in subcortical dopamine, affect latent inhibition.