Major depression is a frequent disease and its lifelong prevalence is estimated around 16.2%
(1). Projections for 2030 rank unipolar depression in the second place of leading causes of
disability adjusted life years (DALYs) worldwide, and it will be the first cause of disability in
high-income countries ahead of cardiovascular diseases (2). In Europe, depression is the
costliest psychiatric disorder (3). Moreover, depressive symptoms are heavily correlated with
other health problems and with increased risk of cardiovascular diseases, Alzheimer disease,
type II diabetes, as well as with higher mortality and noncompliance with medical treatment
(4–8).
Different treatments are available for depressive disorders, but their efficacy is limited, and they
often need some weeks to have a beneficial effect (9). For example, after first-line treatment
with antidepressants drugs only 28% of depressed patients achieve remission (10). Even
though, only one third of patients achieve remission after antidepressant treatment,
antidepressants drugs are the third most prescribed medication in the United States (11).
Pathophysiology of mood disorders is not yet fully understood but significant improvement has
been made with antidepressants and Electroconvulsive therapy (ECT). Different chemical
classes of antidepressants are commercialized including selective serotonin reuptake inhibitors
(SSRIs), norepinephrine reuptake inhibitors (NRIs), serotonin and norepinephrine reuptake
inhibitors (SNRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors
(MAOIs) (12). Another treatment against depression is psychotherapy but, as for
pharmacotherapy, this option has also a limited efficacy and a delayed action (13–15) .
Treatment for depression often combines psychotherapy and antidepressants, but they can be
expensive, and psychotherapy can be difficult to access, due to the cost (16). Hence, there is a
need for new treatments.
Physical activity has been shown to have beneficial effects on depressive symptoms (16). Mood
improvement by exercise is observed in depressed patients, healthy adults and chronically ill
patients (17–19). Moreover, exercise is cheaper and easily accessible compared to
antidepressant treatment and psychotherapy (16). Physical activity has positive effects on
cardiovascular diseases, which are the primary causes of death among patients with major
depressive disorder (4).
The mechanisms underlying the antidepressant effects of physical exercise remain unclear, JL.
Martin and his collaborators have hypothesized that lactate generated during exercise may
have antidepressant effects. The muscles produce lactate during exercise at a relatively high
intensity training. To test their hypothesis, they administered lactate to rodents at a
concentration comparable to that measured during moderate to high intensity exercise (20,21).
Depressive-like behaviour was induced by chronically injecting corticosterone to adult mice.
Previous studies have shown that chronic injections of corticosterone induce symptoms and
neurobiological changes that are similar to those observed in patients with major depression
(22). They found that peripheral administration of lactate produces antidepressant effects in
different animal models of depression (23). In their study, they found an increased expression
of Hes5 in the hippocampus of animals treated with lactate. Hes5 is one of the downstream
effector of the Notch signaling pathway, which is involved in the regulation of adult
hippocampal neurogenesis (AHN). Based on these findings, they examined whether AHN could
be implicated in the antidepressant effects of lactate (23). In this context, they found that chronic
treatment with corticosterone decreased the proliferation of neural progenitors, whereas chronic
lactate administration counteracted the effects of corticosterone (Carrard et al., manuscript in
preparation).
My master project aimed to examine whether lactate counteracts the effects of corticosterone
on the survival of newborn neural cells, another stage involved in AHN.