In a fascinating new study, scientists used pieces of human brain tissue to demonstrate that neural circuits produce electrical patterns very early in the development process, even before senses are active.
These experiments at the University of California, Santa Cruz (UCSC) and other labs suggest that the brain comes with built-in timing rules for thoughts.
Mitochondrial ATP production by oxidative phosphorylation (OXPHOS) is essential for cellular functions, such that mitochondria are known as the powerhouses of the cell (Verschueren et al., 2019). The mitochondrial ETC consists of five enzyme complexes in the inner membrane of the mitochondria. ETC generates a charge across the inner mitochondrial membrane, which drives ATP synthase (complex V) to synthesize ATP from ADP and inorganic phosphate.
Several studies have shown impairments of all five complexes in multiple areas of the AD brain (Kim et al., 2000, 2001; Liang et al., 2008). Mitochondrial dysfunction in AD is apparent from a decrease in neuronal ATP levels, which is associated with the overproduction of ROS, and indicates that mitochondria may fail to maintain cellular energy. A substantial amount of ATP is consumed in the brain due to the high energy requirements of neurons and glia. Since an energy reserve (such as fat or glucose) is not available in the central nervous system (CNS), brain cells must continuously generate ATP to sustain neuronal function (Khatri and Man, 2013). Mitochondria are the primary source of cellular energy production, but aged or damaged mitochondria produce excess free radicals, which can reduce the supply of ATP and contribute to energy loss and mitochondrial dysfunction in AD. Importantly, oxidative damage of the promoter of the gene encoding subunit of the mitochondrial ATP synthase results in reduced levels of the corresponding protein, leading to decreased ATP production, nuclear DNA damage to susceptible genes, and loss of function (Lu et al., 2004; Reed et al., 2008).
In advanced stages of AD, substantial nitration of ATP synthase subunits can take place, leading to the irregular function of the respiratory chain (Castegna et al., 2003; Sultana et al., 2006; Reed et al., 2009). Likewise, ATP-synthase lipoxidation occurs in the hippocampus and parietal cortex of patients with mild cognitive impairment (Reed et al., 2008). Compromised OXPHOS contributes to a characteristic mitochondrial dysfunction in AD brains, leading to decreased ATP production, elevated oxidative stress, and ultimately cell death (Reddy, 2006; Reddy and Beal, 2008; Du et al., 2012). The specific mechanisms of OXPHOS deficiency in AD remain a long-standing scientific question, but the role of mitochondrial F1Fo ATP synthase dysfunction in AD-related mitochondrial OXPHOS failure is emphasized by emerging evidence (Beck et al., 2016; Gauba et al., 2019).
Brain development is a complex process involving, for example, the precise diversification and distribution of cells into distinct areas. The researchers behind the present study have developed a new method called spatial tri-omics, that enables them to simultaneously measure in a specific area of the brain: 1) the activity of genes, 2) how this activity is regulated by epigenetic changes, and 3) if this activity ultimately leads to the production of proteins.
The study is based on analyses of mouse and human brains at different stages of development. The authors generated a spatiotemporal tri-omic atlas of the mouse brain from postnatal day 0 (P0) to P21 and compared corresponding regions with the human developing brain.
“We’ve been able to use this multidimensional method to track brain development over time and map changes from birth to a young age in different parts of the brain, as well as study how the brain reacts to inflammation,” explains the senior author.
Scientists have identified five major “epochs” of human brain development in one of the most comprehensive studies to date of how neural wiring changes from infancy to old age.
The study, based on the brain scans of nearly 4,000 people aged under one to 90, mapped neural connections and how they evolve during our lives. This revealed five broad phases, split up by four pivotal “turning points” in which brain organisation moves on to a different trajectory, at around the ages of nine, 32, 66 and 83 years.
“Looking back, many of us feel our lives have been characterised by different phases. It turns out that brains also go through these eras,” said Prof Duncan Astle, a researcher in neuroinformatics at Cambridge University and senior author of the study.
A discovery from Australian researchers could lead to better treatment for children with neuroblastoma, a cancer that currently claims 9 out of 10 young patients who experience recurrence. The team at the Garvan Institute of Medical Research in Sydney, Australia, found a drug combination that can bypass the cellular defenses these tumors develop that lead to relapse.
In findings made in animal models and published today in Science Advances, Associate Professor David Croucher and his team have shown that a drug already approved for other cancers can trigger neuroblastoma cell death through alternative pathways when the usual routes become blocked. This discovery could lead to better treatment strategies for children whose cancers have stopped responding to standard chemotherapy.
Neuroblastoma is the most common solid tumor in children outside the brain, developing from nerve cells in the adrenal glands above the kidneys or along the spine, chest, abdomen or pelvis. It is typically diagnosed in children under 2 years old. While those with low-risk disease have excellent outcomes, around half of patients are diagnosed with high-risk neuroblastoma—an aggressive form where tumors have already spread. Of these high-risk patients, 15% don’t respond to initial treatment, and half of those who do respond will see their cancer return.
What does it mean that we have consciousness — and why does nature care that we do? In a remarkable new convergence of philosophy, psychology, and comparative neuroscience, researchers at Ruhr University Bochum argue that consciousness is not a mysterious luxury, but a powerful evolutionary adaptation.
According to their analysis, conscious experience first emerged as a mechanism of basic arousal — a primordial alarm system to protect living organisms from immediate danger. ([RUB Newsportal][1]) As evolution proceeded, consciousness evolved further: general alertness enabled organisms to filter through overwhelming flows of sensory data, focus selectively, and detect complex correlations — a capacity indispensable for learning, planning, and survival in a dynamic world.
Finally, in some lineages including our own, a third layer arose: reflexive, self-consciousness. This allows us not only to perceive the world, but to perceive ourselves — our bodies, thoughts, sensations — across time. With it comes memory, foresight, self-awareness, and the ability to integrate personal history into projects and social lives.
What is especially striking: these researchers show that consciousness need not depend on a “human-style” cortex. Studies of birds — whose brain architecture is very different from mammals — reveal comparable functional capacities: sensory awareness, integrated information processing, and even rudimentary forms of self-perception. ([RUB Newsportal][1]) This suggests that consciousness, far from being a human special-case, may be a widespread evolutionary solution — one that can arise in diverse biological substrates when the right functional constraints are met.
In this light, consciousness emerges not as an ineffable mystery or a metaphysical afterthought, but as a natural phenomenon with concrete functions: for feeling, for alertness, for learning, for self-representation. Understanding it may not only tell us who we are — but also why it ever made sense for life to become conscious.
Press Release: Ruhr University Bochum
Researchers around the world are studying how the human brain achieves its extraordinary complexity. A team at the Central Institute of Mental Health in Mannheim and the German Primate Center—Leibniz Institute for Primate Research in Göttingen has now used organoids to show that the ARHGAP11A gene plays a crucial role in brain development. If this gene is missing, key processes involved in cell division and structure become unbalanced.
The human brain distinguishes us from other living beings like no other organ. It enables language, abstract thinking, complex social behavior, and culture. But how can this extraordinarily powerful organ develop, and how is it ensured that nerve cells and supporting cells form in exactly the right places to create the complexity of the human brain?
A team led by Dr. Julia Ladewig at the Central Institute of Mental Health (CIMH) in Mannheim and Dr. Michael Heide at the German Primate Center (DPZ) in Göttingen has investigated this question at the molecular level.
