Week 8

Question 1

Val66Met
* Since the 2003 article this polymorphism has been implicated in **
* **
* ** activity

Answer 1

Val66Met
* Since the 2003 article this polymorphism has been implicated in almost every type of behavioural change and behaviour
* Eating disorders
* Seizure activity

Question 2

The neurotrophic hypothesis
- ** neurons die
- But why? **

Answer 2

The neurotrophic hypothesis
- In the absence of proper neurotrophic support neurons die
- But why? It might be that cells normally are programmed to die and that this pathway is inhibited

Question 3

1. Regular exercise has benefits
   Regular exercise reduces the risk of ** and ** through ** new evidence also suggesting changes to **
   * The effects of regular exercise may be mediated via both a ** (with a subsequent decreased **) and the induction of **
2. Exercise in chronic brain disease
   * Physiologically makes sense that exercise and its effects on inflammation might affect chronic disorders such as , **
   and others
   * However, it has long been known that exercise has a beneficial effect on**
   * Regular exercise and its effect on mood, mood disorders and neurodegeneration have been well studied
   * No biological mechanisms known to underlie this until 2013

Answer 3

1. Regular exercise has benefits
   Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases through anti-inflammatory effects new evidence also suggesting changes to gut microbiome
   * The effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment
2. Exercise in chronic brain disease
   * Physiologically makes sense that exercise and its effects on inflammation might affect chronic disorders such as T2D, CVD
   and others
   * However, it has long been known that exercise has a beneficial effect on mental aspect of health and disease
   * Regular exercise and its effect on mood, mood disorders and neurodegeneration have been well studied
   * No biological mechanisms known to underlie this until 2013

Question 4

1. Muscle myokines – FNDC5
   * Muscle cells ramp up production of a
   protein called ** () during **
   * FNDC5 is a ** with an
   ** (similar to a **)
   * A fragment of this protein (**) gets
   ** and **, where ** drives **
   * The formation of ** to protect against diseases such as **
2. Role of FNDC5 in the brain
   * Other research showed that FNDC5 and ** are expressed **, not just the **, and that both might play a role in the **
   * FNDC5/Irisin was hypothesized to be responsible for **in particular, increased levels of ** essential for maintaining **and **
   * Links between ** and ** levels previously established by numerous labs

Answer 4

1. Muscle myokines – FNDC5
   * Muscle cells ramp up production of a
   protein called FNDC5 (Fibronectin domain-containing protein 5) during exercise
   * FNDC5 is a membrane protein with an
   N-terminal signal peptide (similar to a prohormone)
   * A fragment of this protein (Irisin) gets
   cleaved and released into the bloodstream, where Irisin drives the formation of brown adipose tissue
   * The formation of brown adipose tissue to protect against diseases such as diabetes and obesity
2. Role of FNDC5 in the brain
   * Other research showed that FNDC5 and PGC-1α are expressed in the brain, not just the muscles, and that both might play a role in the development of neurons
   * FNDC5/Irisin was hypothesized to be responsible for exercise- induced benefits to the brain—in particular, increased levels of BDNF essential for maintaining healthy neurons and neurogenesis
   * Links between exercise and BDNF levels previously established by numerous labs

Question 5

Molecules and regulation
- Mice were put on a 30-day endurance training regimen with access to a running wheel ran the equivalent of a 5K every
night
* Mice that engaged in regular exercise had more ** in their ** (responsible for ** and ** and
**)
* Using in vitro models, Wrann et al. (2013) demonstrated that increasing the levels of the ** also increased ** production

Answer 5

Molecules and regulation
- Mice were put on a 30-day endurance training regimen with access to a running wheel ran the equivalent of a 5K every
night
* Mice that engaged in regular exercise had more FNDC5 in their hippocampus (responsible for learning and memory and
neurogenesis)
* Using in vitro models, Wrann et al. (2013) demonstrated that increasing the levels of the co-activator PGC-1α also increased FNDC5 production