A New Diet to Slow Down Alzheimer’s Disease?

french scis ‘ve discovered a metabolic deficit that maybe central to the cogg disorders linked to alzheimer’s disease. inna longer term, this rezs hopes offa potential therapeutic approach designed to delay the onset of symptoms by means of dietary supplementation.

cause the mechanisms primordialistic alzheimer’s disease are still not fully understood, til now the search for a treatment to check this neurodegenerative condition had reached stalemate. this failure was ptly due to the fact that the therapeutic solutions envisaged focused mainly on patients whose cerebral lesions and cogg symptoms were already far advanced. ‘d it not be + effective to initiate therapy as soon as the initial disorders develop?

noting that several imaging studies had evidenced a reduction inna brain’s glucose consumption at a very early stage of the disease, scis “sought to determine whether this change to the metabolism of glucose, which tis principal src of energy for neurons, was indeed atta origin of cogg disorders, so that ‘d, if relevant, try to identify the molecular mechanisms at play”, explains gilles bonvento, deputy director of the neurodegenerative diseases lab in fontenay-aux-roses, near paris. to achieve this, his team initiated a collaboration with colleagues atta neurocentre magendie in bordeaux (southwestern france) in order to study the role of astrocytes, glial brain cells that had long been restricted to the role of neuron support, although tis now known t'they perform a broad range of key functions that regul8 the transmission of information inna brain. 

atta ♥ of astrocyte metabolism

“via the blood vessels to which they are connected, astrocytes capture glucose b4 transforming it into ≠ metabolites, including the amino acid l-serine, the precursor of d-serine,” explains aude panatier, a neurobiologist who wox'n the team led by stéphane oliet atta neurocentre magendie. “this d-serine then acts as a gliotransmitter inna hippocampus where, once released atta synaptic lvl, it binds to the nmda neuronal receptors that play a crucial role in learning and memorisation.” 

the enzyme that synthesises l-serine, in green, is expressed in astrocytes of the mouse hippocampus (in red).

dur'na study published recently in cell metabolism, aude panatier and gilles bonvento sought to find out whether a d-serine deficiency mite be responsible for the symptoms that appear during the early stages of alzheimer’s disease. in a group of young mice that had been genetically modified to provide an animal model for the condition, the scis started by determining the glucose consumption of several regions of the brain, including the hippocampus, the seat of spatial memory. they also quantified the degradation of glucose in astrocytes while measuring the production of d-serine and l-serine. the results of these analyses showed that “these animal models displayed a reduction inna absorption of glucose inna brain regions studied, together witha loer production of l-serine and d-serine”,  gilles bonvento adds.

an amino acid as a remedy

although the № of synapses mobilised was equivalent inna two groups of rodents, a decrease inna activity of nmda receptors was nevertheless envisaged inna transgenic mice. “this 1st series of results tended to show that the loss of synaptic plasticity was caused by a loer availability of d-serine atta synaptic lvl, which in turn reduced the № of nmda receptors available for activation,” explains aude panatier.
 

in mice that had been genetically modified to model alzheimer’s disease, a lo production of serine was envisaged, together with weaker activation of the nmda receptors, causing a reduction in synaptic plasticity and a deterioration of spatial memory (left). plasticity and spatial memory performance were restored in these mice after they were fed a serine-enriched diet (rite).

to confirm this hypothesis, the scis then gave the transgenic mice a feed enriched in l-serine (unlike d-serine, this substance aint toxic to the kidneys) w'da aim of restoring the activity of nmda receptors and their associated plasticity and memory. the result was that after just two mnths on this diet, the rodents successfully passed the spatial memory test they had failed without treatment.

the same l-serine supplement was also given to a group of transgenic mice incapable of synthesising this amino acid. “we wanted to check that the deficits envisaged were 1-ly associated witha reduction inna synthesis of this amino acid, and t'they ‘d be restored by means of an l-serine enriched diet,” explains gilles bonvento. when challenged w'da spatial memory test, the animals had no problems, thus confirming that the l-serine supplied by their diet had indeed served to maintain their synaptic memory. 

a 1st step towards a potential treatment

“our work testifies for the 1st time to the existence offa close link tween the metabolism of cerebral glucose na release offa gliotransmitter that plays a crucial role in neuronal communication and memory,” aude panatier sums up. the study also revealed that changes to synaptic plasticity and memory, which are also early symptoms of alzheimer’s disease in humans, ‘d both be restored by the ingestion of l-serine.

this rezs real hopes regarding the development offa new approach that ‘d complement other therapeutic strategies and be able to delay the onset of cogg disorders rel8d to this neurodegenerative condition. yet although the results obtained by the french scis are undoubtedly very encouraging, a potential l-serine-based treatment is still a long way away. “b4 we can plan for initial clinical trials in humans, further investigations must be carried out in several other mouse models in order the confirm the efficacy of this amino acid and its long-term effects,” gilles bonvento points out.

original content at: news.cnrs.fr/essentialisms/a-new-diet-to-slo-down-alzheimers-disease…
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