Parkinson’s disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic neurons in part of the mid brain called the substantia nigra pars compacta for which there is no cure. Motor symptoms of PD appear at a late stage of the disease while psychiatric disorders known as non-motor symptoms frequently precede motor symptoms by many years.

Prenatal maternal stress, maternal separation or early postnatalstress events have been implicated in the development of psychotic disorderssuch as depression. Stress caused bysocial isolation early in life can affect brain developmentand hence behavior over time. For instance, it has been suggested that children who are maltreated or those who spent early portions of their childhood in institutionsare at risk for developing behavioral and emotional problems.

Therefore, exposure to stress during early life can havelong term effects on brain developmentand these effects include depression. More precisely, early exposure to emotional stress such as maternal separation has been shown tocause long-term neurochemical and behavioral changes later in life.

Depression is commonly associated with Parkinson’s disease(PD) with an estimated prevalence of depression in40 -50 % of PD cases. This high prevalence of depression in PD has prompted the idea that degenerated nigrostriatal system may play a key role in depression.

Mimicking human conditions in animal models

With the advance of the medical research, it is possible to mimic certain human conditions in selected animals, such as mouse or rat, to study the development of a disease and search for treatment. In addition to being very close to the human physiology, these animal models are reliable and critical to develop new treatment strategy and to understand the pathophysiology of a disease.

In the laboratory of Professor Musa V. Mabandla, we havecreated a rat model with depressive-like symptomsby exposing pups to early maternal separation once daily, from post-natal day 1 to 14. We thereafter injected these rat models with depressive-like behaviors with a preclinical dose of 6-hydroxydopamine (a neurotoxin) stereotaxically into the medial forebrain bundle (MFB) to mimic Parkinsonism. This has resulted to a rat model of PD associated with depressive-like behaviors.

We also injected these animal models with Fluvoxamine maleate (FM), an antidepressant widely used for the treatment of psychiatric disorders, to investigate the neuroprotective effects of the drug on a parkinsonian rat model of neurodegeneration.

Our findings show that early maternal separation exacerbated the effects of 6-hydroxydopamine, but FM treatment attenuated neurodegeneration associated with 6-hydroxydopamine toxicity.

Early stress may consequently trigger the symptoms of PD and expose dysfunctions that may have started many years ago. Therefore, irrespective of whether depression is an early symptom of PD or depression is a risk factor for PD, an individual who is depressed engages in behavior that are more likely to result in PD. Fortunately, Fluvoxamine’s ability to attenuate motor deficits associated with psychiatric disorders showed its neuroprotective effect against dopamine neuron degeneration in PD.