Unraveling the role of zinc in memory

Mott, David D.; Dingledine, Raymond

doi:10.1073/pnas.1100323108

Cited by 20 publications

(8 citation statements)

References 14 publications

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“…Haloperidol-induced memory-deficits had been previously documented, therefore the effect seen here is in agreement with those of previous studies that have also reported memory-deficits with repeated haloperidol use [2,54]. On the other hand, Zn had been reported to modulate both ion channels and synaptic plasticity, making it important in both learning and memory [55]. Working-memory is regulated by a number of brain regions (such as hippocampus and prefrontal cortex) through effects of cholinergic, glutamatergic or γ amino butyric acid (GABAergic) projections to these sites [56].…”

Section: Discussionsupporting

confidence: 93%

Zinc Tempers Haloperidol-induced Behavioural Changes in Healthy Mice

Oj¹,

Ayanwale²,

Agoi³

et al. 2016

ijnbs

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Objective: Behavioural changes secondary to haloperidol/zinc administration were studied, with a view to understanding the patterns of behavioural responses that may be exhibited after such treatment in healthy mice. Methodology: 6 month old Swiss mice (24-30 g each, n=12), were given vehicle (distilled water), haloperidol (2 mg/kg), zinc (as Zinc gluconate, 2.5 and 5 mg/kg) or haloperidol/zinc combination, orally for 21 days. Behaviours were assessed after the first and last dose of haloperidol/zinc. Results: Zinc administration led to a significant reduction of haloperidol-induced suppression of horizontal locomotion, rearing and grooming behaviours. Zn also prevented the deterioration in Y-maze and radial-arm maze working-memory that was associated with repeated haloperidol administration. Finally, an enhanced anxiolytic effect was seen with co-administration of haloperidol with the lower dose of zinc. Conclusion: Co-administration of haloperidol with zinc can reduce some unwanted effects that are known to be associated with haloperidol therapy; hence zinc may be a beneficial adjunct to haloperidol administration.

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Section: Discussionsupporting

confidence: 93%

Zinc Tempers Haloperidol-induced Behavioural Changes in Healthy Mice

Oj¹,

Ayanwale²,

Agoi³

et al. 2016

ijnbs

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“…Zinc transporter-3 (ZnT3), Erk1/2 and Creb expression were also reduced (Berbel et al, 2010 ). Zinc and ZnT3 regulate memory formation, acting through the Erk1/2 signaling pathway (Mott and Dingledine, 2011 ). We have found a decreased VGluT1-ir bouton projection area in the stratum lucidum of CA3 in MMI pups compared with C pups.…”

Section: Discussionmentioning

confidence: 99%

Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

et al. 2015

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Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic) and vesicular inhibitory amino acid transporter (VGAT; GABAergic) immunoreactive (ir) boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI) and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism) and E21 (early postnatal hypothyroidism) until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention) and the elevated plus-maze (anxiety-like assessment) tests. The distribution, density and size of VGluT1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism.

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“…The role of zinc in mnemonic processing has been previously explored [85–88], but this is the first report we are aware of showing an effect of zinc supplementation to enhance memory above baseline.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Supplementation with zinc in rats enhances memory and reverses an age-dependent increase in plasma copper

Sandusky‐Beltran

Manchester

McNay

2017

Behavioural Brain Research

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Zinc and copper are essential trace elements. Dyshomeostasis in these two metals has been observed in Alzheimer’s disease, which causes profound cognitive impairment. Insulin therapy has been shown to enhance cognitive performance; however, recent data suggest that this effect may be at least in part due to the inclusion of zinc in the insulin formulation used. Zinc plays a key role in regulation of neuronal glutamate signaling, suggesting a possible link between zinc and memory processes. Consistent with this, zinc deficiency causes cognitive impairments in children. The effect of zinc supplementation on short- and long-term recognition memory, and on spatial working memory, was explored in young and adult male Sprague Dawley rats. After behavioral testing, hippocampal and plasma zinc and copper were measured. Age increased hippocampal zinc and copper, as well as plasma copper, and decreased plasma zinc. An interaction between age and treatment affecting plasma copper was also found, with zinc supplementation reversing elevated plasma copper concentration in adult rats. Zinc supplementation enhanced cognitive performance across tasks. These data support zinc as a plausible therapeutic intervention to ameliorate cognitive impairment in disorders characterized by alterations in zinc and copper, such as Alzheimer’s disease.

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Unraveling the role of zinc in memory

Cited by 20 publications

References 14 publications

Zinc Tempers Haloperidol-induced Behavioural Changes in Healthy Mice

Zinc Tempers Haloperidol-induced Behavioural Changes in Healthy Mice

Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

Supplementation with zinc in rats enhances memory and reverses an age-dependent increase in plasma copper

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