Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc

Abstract

In the central nervous system, certain neurons store zinc within the synaptic vesicles of their axon terminals. This vesicular zinc can then be released in an activity-dependent fashion as an intercellular signal. The functions of vesicular zinc are not entirely understood, but evidence suggests that it is important for some forms of experiencedependent plasticity in the brain. The ability of neurons to store and release vesicular zinc is dependent on expression of the vesicular zinc transporter, ZnT3. Here, we examined the neuronal morphology of mice that lack ZnT3. Brains were collected from mice housed under standard laboratory conditions and from mice housed in enriched environments -large, multilevel enclosures with running wheels, numerous objects and tunnels, and a greater number of cage mates. Golgi-Cox staining was used to visualize neurons for analysis of dendritic length and dendritic spine density. Neurons were analyzed from the barrel cortex, striatum, basolateral amygdala, and hippocampus (CA1). ZnT3 knockout mice, relative to wild type mice, exhibited increased basal dendritic length in the layer 2/3 pyramidal neurons of barrel cortex, independently of housing condition. Environmental enrichment decreased apical dendritic length in these same neurons and increased dendritic spine density on striatal medium spiny neurons. Elimination of ZnT3 did not modulate any of the effects of enrichment. Our results provide no evidence that vesicular zinc is required for the experience-dependent changes that occur in response to environmental enrichment. They are consistent, however, with recent reports suggesting increased cortical volume in ZnT3 knockout mice.

Zinc in the Brain: Friend or Foe?

“…ZnT3 knockout mice showed increased basal dendrite length of layer 2/3 pyramidal neurons of the barrel cortex, as compared to wild-type mice [71].…”

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain

“…Few studies claim the necessity of zinc for experience-dependent plasticity in brain. A study conducted by McAllister et al reported the beneficial effects of EE are independent of zinc in terms of increased basal dendritic length and spine density in neurons of barrel cortex, striatum and amygdala [ 163 ]. Amyloid beta (Aβ) oligomer, a synaptotoxic agent, induced the impairment of LTP through downregulation of miRNA-132 expression and increased histone deacetylase (HDAC3), while EE produced beneficial effects through suppressing the effects of Aβ oligomer in hippocampus of wild-type mice [ 164 ].…”

Study on the mechanism of zinc finger proteins ROCK1 and DMD in zinc-mediated cognitive impairment caused by aluminum exposure

“…Additionally, Al could potentially interfere with the transport and distribution of Zn, hindering its arrival to critical neurons or speci c brain regions. Most notably, Al might disrupt the metabolism and utilization of Zn, resulting in its de ciency or ine cient level in the nervous system (McAllister et al, 2020). Apart from the prior-mentioned studies on the correlation between Al and Zn concentrations, this research further highlights the role of Zn as a pivotal mediator in the relationship between Al exposure and cognitive function.…”