It is well known that nickel (Ni) is an essential element for human and several animal species [
1,
2]. Imbalanced Ni homeostasis either by deficiency or by overload of this metal is associated with organ dysfunction that leads to various physiological and behavioral disorders. Ni deficiency inhibits growth, reduces reproductive rate, and alters glucose and lipid metabolism, which are associated with anemia, alternations of other metal ion contents, and reduced activity of several enzymes in animals [
3]. In contrast, continuous exposure to high levels of Ni leads to multiple toxic effects in various organs, including the lungs, liver, kidneys, and brain [
4,
5,
6].
The nervous system is one of the systems affected by Ni toxicity [
7]. It may be taken up into the brain through failures of the blood–brain barrier (BBB), and also via the olfactory pathway [
8,
9,
10], and then accumulates in the cerebral cortex and whole brain [
8,
11], leading to a cytotoxicity in different types of nerve cells [
7,
11,
12]; a variety of neurological symptoms such as headaches, giddiness, tiredness, lethargy, and ataxia [
6]; apoptosis of olfactory sensory and cerebral cortex neurons and behavioral deficiencies; and disrupts neurotransmitters [
13,
14,
15,
16].
It is known that changes in neurochemistry often correlate with behavioral disturbance [
17]. Animal studies have shown that Ni exposure leads to increased aggressive behavior and affective disorders, and impaired memory processes and exploring activity [
11,
18]. It has been also demonstrated that Ni has a neuromodulatory role; it can interfere with acetylcholine release from peripheral nerve terminals in vitro [
19] and decrease dopamine, norepinephrine, and serotonin levels in certain rat brain regions and change the gene expression of the glutamate receptors [
7,
16,
20,
21].
Among the many mechanisms implicated in nickel-mediated neurotoxicity, oxidative stress has been proposed to play a central role; it can damage tissue, including central nervous system (CNS), leading to impaired neuronal function and alteration in the physicochemical properties of cell membranes, and eventually disrupt the vital functions and overall brain activity [
6,
22]. As a result, it can alter neurotransmission [
23]. Importantly, oxidative stress reduces gamma-Aminobutyric acid (GABA) levels [
24] and alters GABA uptake [
25]. Certain diseases associated with oxidative stress disturbances such as neurodegenerative diseases like Alzheimer’s and Parkinson’s Diseases [
26,
27], and neuropsychiatric diseases including schizophrenia and some forms of behavior, such as aggressiveness, depression, and anxiety, and also to deterioration of short-term spatial memory [
23,
28,
29,
30,
31].
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