Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two debilitating neurodevelopmental disorders. The former is associated with social impairments whereas the latter is associated with inattentiveness, hyperactivity, and impulsivity. There is recent evidence that both disorders are somehow related and that genes may play a large role in these disorders. Despite mounting human and animal research, the neurological pathways underlying ASD and ADHD are still not well understood. Scientists investigate neurodevelopmental disorders by using animal models that have high similarities in genetics and behaviours with humans. Mice have been utilized in neuroscience research as an excellent animal model for a long time; however, the zebrafish has attracted much attention recently, with an increasingly large number of studies using this model. In this review, we first discuss ASD and ADHD aetiology from a general point of view to their characteristics and treatments. We also compare mice and zebrafish for their similarities and discuss their advantages and limitations in neuroscience. Finally, we summarize the most recent and existing research on zebrafish and mouse models of ASD and ADHD. We believe that this review will serve as a unique document providing interesting information to date about these models, thus facilitating research on ASD and ADHD.

The anxiolytic and antidepressant-like activities of the naturally occurring monoterpene 1,8-cineole and its structural isomer 1,4-cineole were evaluated in mice via inhalation administration at doses ranging from 4 × 10⁻⁶ to 4 × 10⁻¹ mg per 400 μL of triethyl citrate. Mice were tested for anxiety-like behaviours by using the light–dark box test (LDB) and marble-burying test (MBT) and for depression-like symptoms by using the forced swimming test (FST) and tail suspension test (TST). Diazepam and fluoxetine were used as standard drugs for anxiolytic and antidepressant tests, respectively. The results showed that 1,8-cineole at 4 × 10⁻⁴ mg, and 1,4-cineole at 4 × 10⁻⁴ and 4 × 10⁻³ mg significantly increased the amount of time spent in the light box and the number of entries in the light box in the LDB as well as reduced the number of marbles buried in the MBT relative to those in the control, suggesting an anxiolytic effect. Similarly, 1,8-cineole at 4 × 10⁻⁴ and 4 × 10⁻² mg and 1,4-cineole at doses of 4 × 10⁻⁴ to 4 × 10⁻² mg significantly reduced immobility times in the FST and TST relative to those of the control, suggesting an antidepressant activity. The role of the GABA_A/benzodiazepine receptor system in the anxiolytic effects of 1,8- and 1,4-cineole was investigated through co-administration of flumazenil, a GABAergic system antagonist. Flumazenil reversed the effects of diazepam and 1,8-cineole, suggesting that 1,8-cineole affects the GABA_A/benzodiazepine receptors. Collectively, the results suggest that inhaled 1,8- and 1,4-cineole prevented anxiety and depressive-like symptoms in classic mice models.

Chromolaena odorata (L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABA_A receptor antagonist, reversed its effects. It was especially interesting to note that β-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.

Lipofuscin, a marker of aging, is the accumulation of autofluorescent granules within microglia and postmitotic cells such as neurons. Lipofuscin has traditionally been regarded as an inert byproduct of cellular degradation. However, recent findings suggest that lipofuscin may play a role in modulating age-related neurodegenerative processes, and several questions remain unanswered. For instance, why do lipofuscin granules accumulate preferentially in aged neurons and microglia? What happens to these pigments upon neuronal demise? Particularly in neurodegenerative diseases like Alzheimer’s disease (AD), why does amyloid β (Aβ) deposition usually begin in late adulthood or during aging? Why do lipofuscin and amyloid plaques appear preferentially in grey matter and rarely in white matter? In this review, we argue that lipofuscin should be revisited not as a simple biomarker of aging, but as a potential modulator of neurodegenerative diseases. We synthesize emerging evidence linking lipofuscin to lysosomal dysfunction, oxidative stress, lipid peroxidation and disease onset—mechanisms critically implicated in neurodegeneration. We also explore the potential interactions of lipofuscin with Aβ and their spatial location, and summarize evidence showing that lipofuscin may influence disease progression via feedback loops affecting cellular clearance and inflammation. Finally, we propose future research directions toward better understanding of the mechanisms of lipofuscin accumulation and improved lysosomal waste clearance in aging.